Dipeptidyl peptidase IV (DPPIV), a member of serine protease, is widely distributed in tissues (e.g., kidney, liver) and plasma and is involved in the metabolism of various physiologically active peptides.
A compound known as a DPPIV inhibitor is (2S,4S)-2-cyano-4-fluoro-1-[(2-hydroxy-1,1-dimethyl)ethylamino]-acetylpyrrolidine (WO02/38541). However, this compound has low solid-state stability in free form, and its salts with mineral or organic acids disclosed in the application are also disadvantageous in terms of low solid-state stability, low stability under humidified conditions and difficulties in their synthesis, etc.
The present invention aims to provide 4-fluoro-2-cyanopyrrolidine derivatives that have an excellent DPPIV inhibition activity as well as physical properties (e.g., stability) required for pharmaceutical preparations.